The carcinoembryonic antigen (CEA) of the colon is a glycoprotein isolated and identified by Gold and his colleagues in 1965, J. Exp. Med. 122, (1965) 467-481. This protein, characteristic of many kinds of cancer tissues, has a molecular weight of about 200,000, Krupey et al. J. Exp. Med. 128 (1968) 387 and Coligan et al. Immunochemistry, 9 (1972) 377. It is rather heterogeneous and 50-75% of its content is of a polysaccharide nature. Great interest in CEA arose as a result of the possibility that its detection or quantitation may serve as an efficient method of cancer diagnosis, Thomson, et al., Proc. Natl. Acad. Sci. USA 64 (1969) 161. Several Radioimmunoassays were developed for the detection of CEA and have been used on tens of thousands of serum samples of cancer patients and normal individuals, Egan et al. Immunochemistry 9 (1972) 289. Many limitations were observed concerning successful use of such radioimmunoassays. These include large numbers of false negative results, as well as cross-reactions with nondigestive-tract cancerous and normal tissues. It has also been reported that in some cases there is an immunological cross-reaction between CEA and blood group substances, Turner et al. J. Immunol. 108 (1972) 1328.
CEA being a glycoprotein, it is reasonable to assume that some of its antigenic determinants may be of polysaccharide nature, whereas others may be of protein nature. Among the protein determinants one might distinguish between sequential ones, namely those that lead to antibodies capable of reacting with a short peptide segment derived from that region of the molecule, and conformation-dependent determinants that lead to the production of antibodies capable of reacting with a certain region of the native protein but that may not react with the protein after its denaturation. In view of the interest in CEA it was thought to be advisable to try to synthesize a portion of the molecule and enquire whether antibodies against such a synthetic material are able to react with either native CEA or its partial degradation products. Terry et al. J. Exp. Med. 136 (1972) 200, reported recently the amino terminal sequence derived from CEA. The sequence found is: Lys-Leu-Thr-Ile-Glu-Ser-Thr-Pro-Phe-Asn-Val-Ala-Glu-Gly-Lys-Glu-VaL-Leu-Le u-Leu-Val-His-Asn-Leu. The same sequence has been found in five other preparations of CEA isolated from tumor tissue.
We have shown previously that it is possible to prepare by stepwise synthesis, a peptide of 19 amino acids corresponding to a portion of the hen egg-white lysozyme moleculre, Arnon et al. Pro.Nat.Acad. Sci. USA 62 (1969) 163. This peptide was attached covalently to a synthetic polymer and the resulting conjugate was shown to provoke antibodies capable of reacting with native lysozyme, Maron et al. Biochem. 10 (1971) 763. In the case of CEA our desire was to prepare a synthetic peptide, convert it into an immunogenic macromolecule and see: (a) whether antibodies to the peptide are capable of recognizing the peptide in intact CEA; (b) whether at least some of the antiboeies made against CEA may recognize the peptide. Should the answer to these two questions be negative, the possibility still remains that whilethe peptide in intact CEA cannot be recognized by antibodies specific to this peptide, nevertheless, the antibodies might recognize the peptide in partial degration products of CEA. It was considered of interest to find out whether antibodies of the peptide could detect some crossreactive material in sera of patients with colonic cancer but not in normal individuals.